Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment

Frontiers in Medicine

Medicine

Adriaan J. van der Meer¹  Bart van Hoek²  Maarten E. Tushuizen²  Anna E. C. Stoelinga²  Leendert A. Trouw³  Michelle D. van den Beukel³  Stef van der Meulen³  Lu Zhang³ 

[1] Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands;Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands;Department of Immunology, Leiden University Medical Center, Leiden, Netherlands;

关键词: autoantibodies;    autoimmune hepatitis;    autoimmune liver disease;    post-translational modifications;    epidemiology;   

DOI  :  10.3389/fmed.2023.1195747

 received in 2023-03-28, accepted in 2023-06-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background(Auto)immune mediated and cholestatic liver disease (AILD) includes autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Especially AIH is characterized by the presence of autoantibodies and elevated serum immunoglobulins. In rheumatoid arthritis, autoantibodies against post-translational modifications (PTMs) such as citrullination (Cit) and carbamylation (CarP) are used as diagnostic and prognostic markers, respectively. We studied the presence of six anti-PTM antibodies in patients with the three AILDs and non-AILD.MethodsAntibodies against six PTMs (malondialdehyde–acetaldehyde adducts (MAA), advanced glycation end-products (AGE), CarP, acetylation (AL), Cit, and nitration (NT)) were tested in sera of patients with AILD (n = 106), non-AILD (n = 101) and compared with healthy controls (HC) (n = 100). Levels and positivity were correlated with clinical and biochemical features in a well-defined cohort of untreated AIH patients.ResultsAnti-PTM antibodies were more often detectable in sera from AILD patients compared with HCs (anti-MAA: 67.9% vs. 2.0%, anti-AGE: 36.8% vs. 4.0%, anti-CarP: 47.2% vs. 5.0% and anti-AL: 18.9% vs. 5.0%). In untreated AIH, time to complete biochemical response (CBR) was associated with anti-MAA, anti-AGE, anti-CarP and anti-AL antibodies. Significantly more patients with at least three anti-PTM antibodies attained CBR at 12  months of treatment (13 vs. 3 p = 0.01).ConclusionAnti-PTM antibodies are frequently present in AILD. The presence of anti-MAA, anti-AGE and anti-CarP antibodies correlates with the presence of AIH within this cohort. In AIH, harboring at least three anti-PTM antibody responses is positively associated with CBR. Determination of anti-PTM antibodies in liver disease may have diagnostic and prognostic value.

【 授权许可】

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Copyright © 2023 van den Beukel, Stoelinga, van der Meer, van der Meulen, Zhang, Tushuizen, van Hoek and Trouw.